JOURNAL OF MOLECULAR STRUCTURE
·
2015
·
IF 1.602
Xiaoming Zhang,Yuyang Tian,Jiangtao Jia,Tingting Zhang,Guangshan Zhu
In this paper we present three new cocrystals based on deferiprone which is the first oral medicine as iron chelator . Solitary deferiprone possesses some known problems due to its good solubility and frequent dosing side effects. For these three novel co crystals, deferiprone is the active pharmaceutical ingredient (API), p -hydroxybenzoic acid (1, C 7 H 9 NO 2 ·C 7 H 6 O 3 ), 2, 5-dihydroxybenzoic acid (2, C 7 H 9 NO 2 ·C 7 H 6 O 4 ) and maleic acid (3, C 7 H 9 NO 2 ·C 4 H 4 O 4 ) are used as cocrystal formers (CCFs), respectively. Their structures were characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD) analysis, thermogravimetric analyses (TGA), differential thermal analysis (DTA), elemental analysis (EA) and infrared spectral analysis (IR). Single crystal X-ray diffraction demonstrates that all three cocrystals (1–3) possess strong hydrogen-bondings assembled through hydroxyl of API and carboxylic acids of CCFs. The PXRD results indicate their high purity of as-synthesized samples. TGA, DTA, EA, IR and dissolution study of API and cocrystals were also measured and discussed, respectively. The results suggest that the cocrystals exhibit low dissolution rates comparing with solitary deferiprone, which is very advantageous for the oral medicine with frequent dosing side effects.
研究领域:
药学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2015
·Vol. 63
·期 2
·68-74
·
IF 1.164
Wen Lv,Lihua Cheng,Baohua Li
One of the major obstacles to successful paclitaxel (PTX) chemotherapy is toxic side effects, which are often due to the conventional surfactants used, such as Cremophor EL. PTX is characterized by its hydrophobicity and insolubility, which limit its application in ovarian cancer therapy. The aim of this study was to develop Cremophor EL-free PTX-loaded methoxy poly(ethylene glycol)-block-(lactic-co-glycolic acid) copolymers (PLGA-mPEG) nanoparticles (NPs) using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a novel emulsifier. The ability of nanoparticles loaded with paclitaxel (NP-PTX) to inhibit tumor growth was assessed in vitro and in vivo. The acute toxicity of NP-PTX was also evaluated in vivo. We found that paclitaxel was efficiently encapsulated into PLGA-mPEG NPs with a low concentration of TPGS as the emulsifier. The synthesized NP-PTX demonstrated the desired diameter of 80 nm as characterized by transmission electron microscopy. The NP-PTX also exhibited a sustained release of loaded PTX over 4 d with the same chemotherapeutic efficiency and reduced side effects. NP-PTX-treated cells showed slightly lower cytotoxic responses compared with those treated with free PTX at the same concentration. In vivo studies confirmed that NP-PTX significantly enhanced the median lethal dose of paclitaxel by 10-fold, and a similar effect on the inhibition of tumor growth was achieved in nude mice.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 8
·2550
·
IF 4.927
Lingzhi Liang,Xia Ren,Junyi Xu,Yurong Ma,Yunlin Xue,Tao Zhuang,Guisen Zhang
Olanzapine is a commonly used drug in the treatment of schizophrenia, but its clinical application has been restricted by metabolic-related side effects. In order to mitigate the weight gain side effects caused by olanzapine, other drugs with different targets were selected for combined use and evaluated in animal models of schizophrenia. SEP-363856 is a novel psychotropic agent which is under phase III clinical trials for schizophrenia treatment. The aim of the research was to evaluate whether co-administration of olanzapine and SEP-363856 exerts synergistic anti-schizophrenic effects in the apomorphine (APO)-induced climbing test, the MK-801-induced hyperactivity test, and the Morris water maze test, and therefore reduces the weight gain side effects induced by olanzapine. Through isobolographic analysis, the results showed a synergistic interaction in the climbing test; the experimental ED30(3 mg/kg) was significantly smaller (p< 0.05) than the theoretical ED30(5 mg/kg). Additionally, such potentiating effects appeared additive in the MK-801 challenge experiment. Co-treatment with an effective dose of olanzapine and a low dose of SEP-363856 reversed MK-801-induced cognitive impairment symptoms in mice. Moreover, combination treatment with olanzapine and SEP-363856 controls sustained weight gain in mice with chronic exposure to olanzapine. These results support further clinical trials to test the effectiveness of co-treatment of olanzapine and SEP-363856 for controlling symptoms and weight gain in patients with schizophrenia during antipsychotic treatments.Keywords:olanzapine;SEP-363856;schizophrenia;synergistic;side effects
研究领域:
神经科学
·
药理学
·
精神病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
·
2014
·
IF 4.558
Jia-Mei Chen,Song Li,Tong-Bu Lu
Cocrystals have been extensively utilized to improve drugs’ properties. Ribavirin is a water-soluble broad-spectrum antiviral drug and its application is severely limited by the peak-to-trough fluctuation in plasma drug concentrations and some undesirable side-effects. We show here that formation of cocrystals may be a useful approach to overcome this problem by reducing the release rate of ribavirin. Three cocrystals of ribavirin with 3,5-dihydroxybenzoic acid (1), gallic acid (2), and barbituric acid (3) were successfully prepared and characterized by powder and single crystal X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis, as well as dynamic vapor sorption measurement. The dissolution process revealed that 1–3 showed a reduced release rate as compared to ribavirin in the buffer solution representing intestinal pH 6.8. This study indicates that the release rate of ribavirin can be manipulated over a wide range by the formation of cocrystals, which may subsequently help lower its peak-to-trough fluctuation in plasma concentrations.
研究领域:
药学
·
药物化学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DELIVERY
·
2016
·
IF 4.843
Aiguo Zeng,Kai Dong,Maoling Wang,Jinyao Sun,Yalin Dong,Ke Wang,Chenning Guo,Yan Yan,Lu Zhang,Xianpeng Shi,Jianfeng Xing
Context: Dexamethasone is the major drug in the treatment of ulcerative colitis (UC). However, the extensive or long-time use of dexamethasone causes many toxic side-effects. Ion exchange resins react with external-ions through their own functional groups and Eudragit S occurs degradation when pH > 7. These features make them suitable for oral delivery system.Objective: Resin microcapsule (DRM) composed by 717 anion exchange resin and Eudragit S100 was used to target dexamethasone to the colon to improve its treatment effect on UC and reduce its toxic side-effects.Results: Dexamethasone sodium phosphate (DXSP) was sequentially encapsulated in 717 anion-exchange resin and Eudragit S100 to prepare the DXSP-loaded resin microcapsule (DXSP-DRM). The in vitro release study and in vivo study of pharmacokinetics and the intestinal drug residues in rat demonstrated the good colon-targeting of DXSP-DRM. Moreover, the DXSP-DRM can reduce the toxic side-effects induced by DXSP and have good therapeutic effects on colitis mouse induced by 2,4,6-trinitrobenzenesulfonic acid.Discussion: Dexamethasone can be targeted to the colon by DRM, thereby enhancing its treatment effect and reducing its toxic side effects.Conclusion: The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeted preparations.
研究领域:
药理学
·
药物递送系统
·
炎症性肠病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 39
·4977-4982
·
IF 2.378
Xiaolin Jiang,Ke Ma,Cuihua Hu,Mingyan Gao,Jiashuo Zhang,Ying Wang,Yujuan Chen,Zhengxun Song,Zuobin Wang
Atomic force microscopy (AFM) can be used to obtain the physical information of single live cancer cells; however, the physical changes in live cells with time based on AFM remain to be studied, which play a key role in the evaluation of the efficacy and side effects of drugs. Herein, the treatment of the A549 cell line with the anticarcinogen 5-fluorouracil has been discussed based on the AFM analysis of their continuous physical changes, including their surface morphology, height, adhesion and Young's modulus, with time. In comparison, the African green monkey kidney (Vero) cell line was tested as normal cells to determine the side effects of 5-fluorouracil. The results show that the optimal concentration of 5-fluorouracil is about 500 μM, which presents the best anticancer effect and mild side effects.
研究领域:
生物医学工程
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Cong Wang,Wenting Liu,Yong Huang,Lin Zheng,Lili Wang,Ruixi Li,Chang Yang
Risedronate sodium (RIS) is a primary treatment for postmenopausal osteoporosis, but oral administration requires patients to remain upright to prevent side effects like esophagitis, gastritis, and ulcers, which can be difficult for those with fatigue or bone pain. This study developed RIS-loaded Bletilla striata polysaccharide microneedles (RIS-BMNs) with sufficient mechanical strength for effective skin penetration and drug delivery. Franz diffusion cell experiments showed that RIS-BMNs achieved 3 times higher in vitro transdermal absorption than the RIS solution and 2.6 times more than RIS patches. The stimulation test found that RIS-BMNs caused minimal skin irritation, which resolved within 12 h. RIS-BMNs also promoted cell proliferation and wound healing, as shown by in vitro cell viability and migration tests, and improved bone trabeculae and density in osteoporotic rats, according to micro-CT imaging and H&E staining. Biochemical markers (BGP, IL-6, CTX-I, TRAP, OPG, and PINP) indicated that RIS-BMNs had anti-osteoporotic effects comparable to oral RIS but without gastrointestinal side effects, as confirmed by H&E staining. Our new transdermal method for RIS could improve adherence in treating postmenopausal osteoporosis.
研究领域:
药剂学
·
药物递送系统
·
透皮技术
·
骨骼健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2017
·
IF 2.295
Kai Dong,Hefeng Zhang,Yan Yan,Jinyao Sun,Yalin Dong,Ke Wang,Lu Zhang,Xianpeng Shi,Jianfeng Xing
Context: Extensive or long-time use of corticosteroids often causes many toxic side-effects. The ion exchange resins and the coating material, Eudragit, can be used in combination to form a new oral delivery system to deliver corticosteroids.Objectives: The resin microcapsule (DRM) composed by Amberlite 717 and Eudragit S100 was used to target hydrocortisone (HC) to the colon in order to improve its treatment effect on ulcerative colitis (UC) and reduce its toxic side-effects.Methods: Hydrocortisone sodium succinate (HSS) was sequentially encapsulated in Amberlite 717 and Eudragit S100 to prepare the HSS-loaded resin microcapsule (HSS-DRM). The scanning electron microscopy (SEM) was employed to investigate the morphology and structure of HSS-DRM. The in vitro release and in vivo studies of pharmacokinetics and intestinal drug residues in rat were used to study the colon-targeting of HSS-DRM. The mouse induced by 2,4,6-trinitrobenzenesulfonic acid was used to study the treatment of HSS-DRM on experimental colitis.Results: SEM study showed good morphology and structure of HSS-DRM. In the in vitro release study, > 80% of HSS was released in the colon environment (pH 7.4). The in vivo studies showed good colon-targeting of HSS-DRM (Tmax = 0.97 h, Cmax = 118.28 µg/mL of HSS; Tmax = 2.16 h, Cmax = 64.47 µg/mL of HSS-DRM). Moreover, the HSS-DRM could reduce adverse reactions induced by HSS and had good therapeutic effects on the experimental colitis.Conclusions: The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeting preparations.
研究领域:
药剂学
·
消化病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Yuman Dong,Peng Liu
Efficient approach was established to improve the drug delivery performance of the pH-triggered prodrug nanoparticles by introducing a polycation block as a pH-sensitive gatekeeper. With the help of the poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) block as a pH-sensitive shell gatekeeper, the proposed core-shell-corona PEG 43 - b -PDPA 65 - b -PFPMA 36 -DOX nanoparticles possessed a higher drug release rate in the simulated acidic tumor intracellular micro-environment while a lower premature drug leakage in the simulated weak basic normal physiological medium, compared with the core-shell PEG 43 - b -PFPMA 36 -DOX nanoparticles. The proposed strategy is expected to design high-performance drug delivery systems (DDSs) for tumor treatment, with improved anticancer efficacy but minimized toxic side effects.
研究领域:
药物递送
·
生物材料
·
肿瘤治疗
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Hailong Tian,Jing Zhang,Huiyuan Zhang,Yue Jiang,Aixin Song,Yuxia Luan
The side effects of anticancer drugs and tumor tolerance from heat shock protein expression are still a bottleneck for the current chemo-phototherapy. Although quercetin (Qu) is a naturally low-side effect anticancer drug and heat shock protein inhibitor for tailoring phototherapy, it is largely restricted by poor water solubility. Moreover, the near-infrared dye IR780-iodide (IR780), as a promising phototherapy agent, is also restricted from clinical applications due to its poor water solubility. Herein, we rationally designed a robust low side-effect and heat-shock protein-inhibited chemo-phototherapy nanoplatform via co-assembly of biotin-tailored IR780 (B780) and quercetin, defined as B780/Qu nanoparticles (B780/Qu NPs), which efficiently solved the poor water solubility of both IR780 and Qu. Moreover, the B780 endowed B780/Qu NPs with superior active tumor-targeted property and pH-responsive drug delivery. Thanks to the combination of chemo-phototherapy, the B780/Qu NPs with near infrared (NIR) laser irradiation exhibited excellent anti-tumor efficacy. Therefore, our B780/Qu NPs are very promising as an efficient low side-effect and heat-shock protein-inhibited chemo-phototherapy nanoplatform against tumors.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Chan Yu,Qing Zhou,Fan Xiao,Yihui Li,Hang Hu,Ying Wan,Zifu Li,Xiangliang Yang
Doxorubicin (DOX), a kind of wide-spectrum chemotherapeutic drug, can cause severe side effects in clinical use. To enhance its antitumor efficacy while reducing the side effects, two kinds of nanoparticles with desirable compositions and properties were assembled using optimally synthesized hydroxyethyl starch-grafted-polylactide (HES-g-PLA) copolymers and utilized as partner nanocarriers. The large empty HES-g-PLA nanoparticles (mean size, ca. 700 nm), at an optimized dose of 400 mg/kg, were used to block up the reticuloendothelial system in tumor-bearing mice 1.5 h in advance, and the small DOX-loaded HES-g-PLA nanoparticles (mean size, ca. 130 nm) were subsequently applied to the mice. When these partner nanocarriers were administered in this sequential mode, the released DOX had a significantly prolonged plasma half-life time and much slower clearance rate as well as a largely enhanced intratumoral accumulation as compared to free DOX. In vivo antitumor studies demonstrated that the DOX-loaded HES-g-PLA nanoparticles working together with their partner exhibited remarkably enhanced antitumor efficacy in comparison to free DOX. In addition, these HES-g-PLA partner nanocarriers showed negligible damage to the normal organs of the treated mice. Considering safe and efficient antitumor performance of DOX-loaded HES-g-PLA nanoparticles, the newly developed partner nanocarriers in combination with their administration mode have promising potential in clinical cancer chemotherapy.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yixuan Wang,Sisi Cao,Kaiyue Yu,Fengdie Yang,Xiuming Yu,Yuanhao Zhai,Chuanbin Wu,Yuehong Xu
Background: Topical application of tacrolimus (FK506) was effective in treating atopic dermatitis (AD); however, the therapeutic efficiency is hampered by its poor penetration into the skin and local side effects of transient irritation symptoms with a burning sensation, a feeling of warmth or heat. Menthol and camphor have been widely used in topical compound formulations for adjunctive pharmacotherapy for antipruritics and analgesics owing to their cool nature, and both present skin penetration enhancing effects. Moreover, they can form a liquid eutectic oil to solubilize hydrophobic drugs.Purpose: Taking advantages of menthol/camphor eutectic (MCE), this work aims to integrate FK506 into MCE to construct a microemulsion system, i.e., FK506 MCE ME, which simultaneously enhances the percutaneous delivery and treatment efficacy, while reduces the side effects of FK506.Methods: The formulation of FK506 MCE ME was optimized and characterized. Different formulations containing FK506 were topically administered to treat 1–chloro–2, 4–dinitrobenzene (DNCB)-induced murine AD.Results: MCE solubilized FK506. FK506 in MCE ME penetrated skin in vitro more than in the commercial ointment, and MCE predominantly exerted the enhancing effects in MCE ME. FK506 MCE ME or FK506 MCE ME gel had greater effects on clinical symptoms, histological analysis, and IgE than did commercial FK506. The anti-pruritic and down-regulation of substance P effects of MCE ME vehicle mitigated the side effects of FK506 application.Conclusion: MCE ME presented the excellent properties of simultaneously enhancing the percutaneous delivery and treatment efficacy, while reducing the side effects of FK506 for AD. Therefore, MCE ME is a promising nanoscale system for FK506 to effectively treating AD with low irritation and high medication adherence.Chemical compounds studied in this article: Tacrolimus (PubChem CID: 445643); menthol (PubChem CID: 1254); camphor (PubChem CID: 2537)
研究领域:
药剂学
·
皮肤科
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）